Effect of Piflutixol on Turnover of Catecholamines in Mouse Brain and Rat Corpus Striatum

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Abstract
Dopamine metabolism in vivo was studied after treatment with piflutixol (6-fluoro-9-[3-(4-(2-hydroxyethyl)piperidino)propylidene]-2-trifluoromethyl-thioxanthene) a novel thioxanthene derivative with potent neuroleptic properties and sedative effects. In mice piflutixol increased both noradrenaline [norepinephrine] (NA) and dopamine (DA) turnover rate measured as increased disappearance of 14C-amines formed from 14C-L-tyrosine. The ratio between the minimal effective doses for 14C-NA and 14C-DA disappearance was 2, which is of the same order of magnitude as obtained with cis(Z)-chlorprothixene, pimozide and chlorpromazine. After 14C-L-tyrosine the accumulation of 14C-dopamine was initially increased after which it decreased from day 4-5. These changes resemble those obtained after other neuroleptics and parallel the initial receptor blockade and the subsequent receptor supersensitivity found in pharmacological experiments. Piflutixol induced a rapid increase in both DOPAC [3,4-dihydroxyphenylacetic acid] and HVA (homovanillic acid) with a maximal effect after 2-6 h. After 2-3 days the levels had returned to normal. The doses of piflutixol which at 24 h doubled the levels of DOPAC and HVA were found to be 0.055 and 0.021 mg/kg s.c., respectively. Piflutixol is a powerful and long lasting DA receptor blocking agent, which changes the synthesis and release of DA in a way similar to basic neuroleptics.